Preparation of tricyclic enones as templates for stereocontrolled natural product synthesis

Persistent Link:
http://hdl.handle.net/10150/282796
Title:
Preparation of tricyclic enones as templates for stereocontrolled natural product synthesis
Author:
Baron, James Andrew, 1971-
Issue Date:
1998
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Small cycloalkanones with adjacent fused cyclopropane rings are excellent substrates for highly diastereoselective (α'-alkylations of enolates derived from these systems. Diastereoselectivity can be attributed to steric interactions between the cyclopropane endo methylene hydrogen and the incoming electrophile, since this atom shields the face of the enolate cis to the cyclopropane. Monoalkylation of enolates derived from bicyclo[3.1.0]hexan-2-one, bicyclo[4.1.0]heptan-2-one and bicyclo[5.1.0]octan-2-one with general electrophiles resulted in the corresponding 3-alkylated cyclopropyl ketone derivatives in synthetically useful yields. Diastereoselectivities for these systems ranged from 4:1 for six-membered cyclopropyl ketones to >20:1 for five- and seven-membered cyclopropyl ketones. Enolates derived from these 3-alkylated cyclopropyl ketones exhibited similar diastereoselectivities and yields to give the corresponding 3,3-dialkylated derivatives when alkylated with similar electrophiles. The relative stereochemistry of alkylation was determined to be trans to the cyclopropane through analysis of anisotropic shielding interactions between alkyl side chains containing phenyl rings and the endo protons on the cyclopropane carbon. This relative stereochemistry can be controlled by the sequence of alkylation, since reversal in the alkylative steps results in an inversion at the newly formed quaternary center. Synthesis of tricyclic enones was carried out through application of this (α'-alkylation methodology using electrophiles that could later be modified to give the corresponding 1,3- and 1,4-cyclopropyl diketones. Cyclization of these diketone intermediates through intramolecular aldol condensations resulted in a series of tricyclic enones whose ring junction relative stereochemistry is controlled through correct ordering of electrophiles in the alkylation steps. The result is a broadly applicable toolbox of annulated materials that can be applied towards the synthesis of natural products containing fused five- and six-membered rings with a defined stereochemistry at the ring junction.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Chemistry, Organic.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Chemistry
Degree Grantor:
University of Arizona
Advisor:
Mash, Eugene A.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titlePreparation of tricyclic enones as templates for stereocontrolled natural product synthesisen_US
dc.creatorBaron, James Andrew, 1971-en_US
dc.contributor.authorBaron, James Andrew, 1971-en_US
dc.date.issued1998en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractSmall cycloalkanones with adjacent fused cyclopropane rings are excellent substrates for highly diastereoselective (α'-alkylations of enolates derived from these systems. Diastereoselectivity can be attributed to steric interactions between the cyclopropane endo methylene hydrogen and the incoming electrophile, since this atom shields the face of the enolate cis to the cyclopropane. Monoalkylation of enolates derived from bicyclo[3.1.0]hexan-2-one, bicyclo[4.1.0]heptan-2-one and bicyclo[5.1.0]octan-2-one with general electrophiles resulted in the corresponding 3-alkylated cyclopropyl ketone derivatives in synthetically useful yields. Diastereoselectivities for these systems ranged from 4:1 for six-membered cyclopropyl ketones to >20:1 for five- and seven-membered cyclopropyl ketones. Enolates derived from these 3-alkylated cyclopropyl ketones exhibited similar diastereoselectivities and yields to give the corresponding 3,3-dialkylated derivatives when alkylated with similar electrophiles. The relative stereochemistry of alkylation was determined to be trans to the cyclopropane through analysis of anisotropic shielding interactions between alkyl side chains containing phenyl rings and the endo protons on the cyclopropane carbon. This relative stereochemistry can be controlled by the sequence of alkylation, since reversal in the alkylative steps results in an inversion at the newly formed quaternary center. Synthesis of tricyclic enones was carried out through application of this (α'-alkylation methodology using electrophiles that could later be modified to give the corresponding 1,3- and 1,4-cyclopropyl diketones. Cyclization of these diketone intermediates through intramolecular aldol condensations resulted in a series of tricyclic enones whose ring junction relative stereochemistry is controlled through correct ordering of electrophiles in the alkylation steps. The result is a broadly applicable toolbox of annulated materials that can be applied towards the synthesis of natural products containing fused five- and six-membered rings with a defined stereochemistry at the ring junction.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectChemistry, Organic.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineChemistryen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorMash, Eugene A.en_US
dc.identifier.proquest9912099en_US
dc.identifier.bibrecord.b39122888en_US
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